Role of Host Cell Factor-1 in cell cycle regulation.

Abstract

Host cell factor-1(HCF-1) was first discovered as a cellular cofactor in the VP16-induced complex, a multi-protein DNA complex that forms on immediate early gene promoters of herpes simplex virus (HSV) to activate viral gene transcription. Subsequent research has revealed HCF-1 to be an abundant chromatin-associated protein that regulates various stages of the cell cycle. Recent reports show that HCF-1 interacts with diverse E2F proteins to induce cell-cycle-specific transcription. HCF-1 can act as a scaffold to a variety of histone-modifying proteins and these HCF-1-E2F-containing multi-protein complexes can bring about context-dependent activation or repression of transcription. In this review we examine the diversity of HCF-E2F interactions and the variety of multi-protein complexes it occurs in, to influence the local chromatin landscape at the E2F-promoters.

Mixed Lineage Leukemia 5 (MLL5) Protein Regulates Cell Cycle Progression and E2F1-responsive Gene Expression via Association with Host Cell Factor-1 (HCF-1)

“…The HCF-1 protein was discovered originally as a host cell factor for human herpes simplex virus infection, and later stud- ies indicated that HCF-1 plays a key role in cell-cycle progression, partially through its interactions with various members of the E2F transcription factor family to induce cell cycle-specific transcription (22,26). In this study, we further showed that MLL5 could associate with HCF-1 within the nucleus, and a previously unknown HBM motif in the MLL5 protein mediated the interaction with the Kelch domain of the HCF-1 protein.…”

“…HCF-1 was originally discovered as a host cell factor for human herpes simplex virus infection, and it plays a crucial role in transcriptional regulation at specific cell-cycle phases (22). HCF-1-Pro protein undergoes a post-translationally proteolytic maturation process and results in two stably associated HCF-1-N and HCF-1-C fragments (23).…”

The potential role of O-GlcNAc modification in cancer epigenetics

“…Recent findings indicate that pRb and HCF-1 can bind to E2F1 simultaneously. They form repressive (pRb) to activating (HCF-1) transition complex during the G1 to S phase progression [82]. O-GlcNAcylation may be involved in these interactions.…”

“…HCF-1 is overexpressed in cancers and this is one of the markers of a poor prognosis in cancer treatment [83]. HCF-1 is also a key regulatory factor in many important processes, like embryonic stem cell pluripotency, stress responses, and development [82]. HCF-1 undergoes a specific process of proteolytic maturation.…”

“…It is an abundant chromatin-associated protein that regulates multiple steps in cell cycle progression [82]. HCF-1 is overexpressed in cancers and this is one of the markers of a poor prognosis in cancer treatment [83].…”